A phase II trial of Cremorphor EL-free paclitaxel (Genexol-PM) and gemcitabine in patients with advanced non-small cell lung cancer

Abstract

PurposeGenexol-PM is a Cremorphor EL (CrEL)-free polymeric micelle formulation of paclitaxel that allows higher-dose administration with less hypersensitivity. This study was designed to evaluate the efficacy and safety of Genexol-PM and gemcitabine combination in advanced non-small cell lung cancer patients as a first-line treatment.Patients and methodsThis is a prospective, single-arm, single-center phase II study. Patients with advanced NSCLC received Genexol-PM at 230 mg/m2 on day 1 and gemcitabine 1,000 mg/m2 on day 1 and day 8 of a 3-week cycle. Six cycles of chemotherapy were planned unless there was disease progression. The primary endpoint was overall response rate.ResultsForty-three patients received the study drugs with a median of 4 cycles per patient (range 1–6). The overall response rate was 46.5 %. The median progression-free survival was 4.0 months (95 % CI 2.0–6.0 months), and median overall survival was 14.8 months (95 % CI 9.1–20.5 months). The most common toxicities were anemia (n = 29, 67 %), asthenia (n = 17, 40 %), myalgia (n = 16, 37 %), peripheral neuropathy (n = 15, 35 %), and diarrhea (n = 12, 30 %). The most common grade 3/4 adverse events were neutropenia (n = 7, 16 %) and pneumonia (n = 5, 12 %). Two patients died of pneumonia and dyspnea.ConclusionsCrEL-free paclitaxel in combination with gemcitabine demonstrated favorable antitumor activity with little emetogenicities in non-small cell lung cancer patients. However, frequent grade 3/4 toxicities were observed, and safety should be evaluated thoroughly in future studies.

Sensory neuron subpopulation-specific dysregulation of intracellular calcium in a rat model of chemotherapy-induced peripheral neuropathy

“…More importantly, there is evidence suggesting that the paclitaxel vehicle may be responsible for some of the side effects of the chemotherapy treatment (Gelderblom et al, 2001, Ahn et al, 2014). We therefore assessed the impact of vehicle on resting [Ca 2+ ] i and evoked transients in subpopulations of putative nociceptive neurons defined by target of innervation.…”

Cancer nanomedicine: progress, challenges and opportunities

“…Although the every-3-week dosing schedule of nab-paclitaxel is superior to paclitaxel in terms of response rate and time to progression for patients with breast cancer 19 , a once-per-week dosing schedule did not show similar trends in progression-free survival (PFS) or OS and furthermore, showed increased toxicity 20 . Polymeric micelles (for example, Genexol-PM 21 and NK105 (REF. 22)) and polymeric NPs (for example, CRLX101 (REF.…”

Liver-targeting self-assembled hyaluronic acid-glycyrrhetinic acid micelles enhance hepato-protective effect of silybin after oral administration

“…For example, the micellar formulations, NK911 and Genexol-PM, have already advanced to the clinical trials (Matsumura, 2006;Ahn et al, 2014). Thanks to their distinctive core-shell structure, polymeric micelles possess high loading capacity of poorly water-soluble drugs within the hydrophobic inner core; whereas the hydrophilic corona confers aqueous solubility and steric stability, which also protects the encapsulated drug from inactivation in gastrointestinal components (Croy & Kwon, 2006;Liang et al, 2015).…”